Design, molecular modeling, synthesis, and anti-HIV-1 activity of new indolyl aryl sulfones. Novel derivatives of the indole-2-carboxamide.

Molecular modeling studies and an updated highly predictive 3-D QSAR model led to the discovery of exceptionally potent indolyl aryl sulfones (IASs) characterized by the presence of either a pyrrolidyn-2-one nucleus at the indole-2-carboxamide or some substituents at the indole-2-carbohydrazide. Compounds 7 and 9 were found active in the sub-nanomolar range of concentration in both MT-4 and C8166 cell-based anti-HIV assays. These compounds, and in particular compound 9, also showed excellent inhibitory activity against both HIV-112 and HIV-AB1 primary isolates in lymphocytes and against HIV WT in macrophages.

• Publication year

  2006

• Venue

  Journal of Medicinal Chemistry

• Publication date

  2006-05-03

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1021/JM0512490PMID 16722636
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Synthesis of novel 1,5-diarylpyrazole-3-carboxamide derivatives and their biological activities

  2006cited by this paper
• Indolyl Aryl Sulphones as HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: Synthesis, Biological Evaluation and Binding Mode Studies of New Derivatives at Indole-2-carboxamide

  2006cited by this paper
• Docking and 3-D QSAR studies on indolyl aryl sulfones. Binding mode exploration at the HIV-1 reverse transcriptase non-nucleoside binding site and design of highly active N-(2-hydroxyethyl)carboxamide and N-(2-hydroxyethyl)carbohydrazide derivatives.

  2005cited by this paper
• HIV-reverse transcriptase inhibition: inclusion of ligand-induced fit by cross-docking studies.

  2005cited by this paper
• Non‐Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): Past, Present, and Future

  2004cited by this paper
• Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved drug resistance properties. 1.

  2004cited by this paper
• Simple, short peptide derivatives of a sulfonylindolecarboxamide (L-737,126) active in vitro against HIV-1 wild type and variants carrying non-nucleoside reverse transcriptase inhibitor resistance mutations.

  2004cited by this paper
• Novel indolyl aryl sulfones active against HIV-1 carrying NNRTI resistance mutations: synthesis and SAR studies.

  2003cited by this paper
• Announcing the worldwide Protein Data Bank

  2003cited by this paper
• ENFUVIRTIDE (FUZEON®): THE FIRST FUSION INHIBITOR

  2003cited by this paper
• The effect of NNRTIs on HIV reverse transcriptase dimerization.

  2003cited by this paper
• Enfuvirtide (Fuzeon): the first fusion inhibitor.

  2003cited by this paper
• Discovery of second generation quinazolinone non-nucleoside reverse transcriptase inhibitors of HIV-1.

  2002cited by this paper
• 2-Amino-6-arylsulfonylbenzonitriles as non-nucleoside reverse transcriptase inhibitors of HIV-1.

  2001cited by this paper
• Estimation of Aqueous Solubility of Chemical Compounds Using E-State Indices

  2001cited by this paper
• Structure-based design, synthesis, and biological evaluation of novel pyrrolyl aryl sulfones: HIV-1 non-nucleoside reverse transcriptase inhibitors active at nanomolar concentrations.

  2000cited by this paper
• Antimycobacterial pyrroles: synthesis, anti-Mycobacterium tuberculosis activity and QSAR studies.

  2000cited by this paper
• Anti-Human Immunodeficiency Virus Drug Combination Strategies

  1998cited by this paper
• A strategy for the incorporation of water molecules present in a ligand binding site into a three-dimensional quantitative structure--activity relationship analysis.

  1997cited by this paper
• Resistance to nevirapine of HIV-1 reverse transcriptase mutants: loss of stabilizing interactions and thermodynamic or steric barriers are induced by different single amino acid substitutions.

  1997cited by this paper
• Smart region definition: a new way to improve the predictive ability and interpretability of three-dimensional quantitative structure-activity relationships.

  1997cited by this paper
• APOPTOSIS OF HUMAN MONOCYTES/MACROPHAGES IN MYCOBACTERIUM TUBERCULOSIS INFECTION

  1997cited by this paper
• Molecular modeling of azole antifungal agents active against Candida albicans. 1. A comparative molecular field analysis study.

  1996cited by this paper
• Automated docking of flexible ligands: Applications of autodock

  1996cited by this paper
• 5H-pyrrolo[1,2-b] [1,2,5]benzothiadiazepines (PBTDs): a novel class of non-nucleoside reverse transcriptase inhibitors.

  1996cited by this paper
• 2-Sulfonyl-4-chloroanilino moiety: a potent pharmacophore for the anti-human immunodeficiency virus type 1 activity of pyrrolyl aryl sulfones.

  1996cited by this paper
• 2-Heterocyclic indole-3-sulfones as inhibitors of HIV-1 reverse transcriptase

  1995cited by this paper
• AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules

  1995cited by this paper
• Cystamine potently suppresses in vitro HIV replication in acutely and chronically infected human cells.

  1994cited by this paper
• Sensitivity of wild-type human immunodeficiency virus type 1 reverse transcriptase to dideoxynucleotides depends on template length; the sensitivity of drug-resistant mutants does not.

  1994cited by this paper
• 5-chloro-3-(phenylsulfonyl)indole-2-carboxamide: a novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase.

  1993cited by this paper
• Generating Optimal Linear PLS Estimations (GOLPE): An Advanced Chemometric Tool for Handling 3D‐QSAR Problems

  1993cited by this paper
• Efficient and reproducible new semimicromethod for the detection and titration of HIV in human plasma

  1992cited by this paper
• Macromodel—an integrated software system for modeling organic and bioorganic molecules using molecular mechanics

  1990cited by this paper
• Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds.

  1988cited by this paper
• Inhibition of human immunodeficiency virus (HIV-1/HTLV-IIIBa-L) replication in fresh and cultured human peripheral blood monocytes/macrophages by azidothymidine and related 2',3'- dideoxynucleosides

  1988cited by this paper
• A computational procedure for determining energetically favorable binding sites on biologically important macromolecules.

  1985cited by this paper
• Trans-acting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells.

  1984cited by this paper
• Derivation and properties of Michaelis-Menten type and Hill type equations for reference ligands.

  1976cited by this paper

• Dietary Supplementation with a 3-Selenoureidoindole Derivative Enhances Thermotolerance and Modifies the Hemolymph Amino Acid Profile in Silkworm (Bombyx mori)

  2026cites this paper
• Precise Manipulation on Effects of Framework Microenvironment in Covalent Triazine Frameworks for Efficient Photocatalytic C3–H Thiocyanation of Indoles

  2025cites this paper
• Iodine‐Catalyzed C3–H Sulfinylation of Indoles with Sulfenamides

  2025cites this paper
• Synthesis of 1,2-Disubstituted-3-thioindoles by the Madelung Reaction

  2025cites this paper
• Synthesis and evaluation of tetrahydrobenzo[cd]indole derivatives as glycogen phosphorylase inhibitors

  2025cites this paper
• Regioselective sulfenylation of indoles using sulfonyl hydrazides: In silico design, DFT calculation, hirshfeld surface analysis, ADMET study, molecular docking and anticancer activity

  2025cites this paper
• Recent Progress of Visible Light-Induced the Synthesis of C(3) (Hetero)arylthio Indole Compounds

  2024cites this paper
• Design, Synthesis, In-Silico and Cytotoxic Studies of Indole Derivatives as Potent BCL-2 Inhibitors

  2024cites this paper
• Synthesis of Novel Indolyl Aryl Sulfone-clubbed Hydrazone Derivatives as Potential HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: Molecular Modeling and QSAR Studies.

  2024cites this paper
• Iodophor-catalyzed sulfenylation of indoles with sulfonyl hydrazides for the synthesis of 3-sulfenylindoles

  2024cites this paper
• Regioselective Thiolation of Indoles with Sulfinyl Amides

  2024cites this paper
• Recent advances in the radical cascade reaction for constructing nitrogen heterocycles using azides as radical acceptors.

  2024cites this paper
• Simple and efficient synthesis of pyrrolo[3,2‐f]quinoxaline derivatives via three‐component reaction

  2024cites this paper
• Selective Synthesis of 3‐Chalcogenylindoles via Silver‐Catalyzed Direct Chalcogenation of Indoles with Dichalcogenides

  2023cites this paper
• Dehydroxylative Sulfonylation of Alcohols.

  2023cites this paper
• Synthesis and Biological Screening of Novel Indole-derived Imidazo[2,1-b][1,3,4]thiadiazoles as EGFR Targeting Anticancer Agents

  2023cites this paper
• Synthesis and investigation of new indole‐containing vinyl sulfide derivatives: In silico and in vitro studies for potential therapeutic applications

  2023cites this paper
• Dehydroaromatization of Indolines and Cyclohexanones with Thiol Access to Aryl Sulfides under Basic Conditions.

  2023cites this paper
• A Useful Methods of Direct Sulfenylation at the 3-Position of Indoles Employing various Sulfenylating Agents

  2022cites this paper
• Visible-Light-Induced, Graphene Oxide-Promoted C3-Chalcogenylation of Indoles Strategy under Transition-Metal-Free Conditions

  2022cites this paper
• DBU-Catalyzed Aerobic CDC Reaction of Thiophenols.

  2022cites this paper
• Boosted Heterogeneous Catalysis by Surface‐Accumulated Excess Electrons of Non‐Oxidized Bare Copper Nanoparticles on Electride Support

  2022cites this paper
• Visible-light-induced indole synthesis via intramolecular C–N bond formation: desulfonylative C(sp2)–H functionalization

  2022cites this paper
• Synthesis of 1,2,6-trisubstituted indoles from 6-propargylcyclohex-2-enones and primary amines

  2022cites this paper
• Synthesis, Spectroscopic, Characterization and X-ray Structures of Lanthanide(III) Complexes Derived from 1,5-bis(phenyl(pyridin-2-yl)methylene)carbonohydrazide

  2022cites this paper
• An Interrupted Pummerer Reaction Mediated by a Hypervalent Iodine(III) Reagent: In Situ Formation of RSCl and Its Application for the Synthesis of 3-Sulfenylated Indoles.

  2021cites this paper
• University of Birmingham Gold(I)-catalyzed synthesis of 3-sulfenyl pyrroles and indoles by a regioselective annulation of alkynyl thioethers

  2021cites this paper
• Recent developments by zinc based reagents/catalysts promoted organic transformations

  2021cites this paper
• Microwaves assisted synthesis of antitumor agents of novel azoles, azines, and azoloazines pendant to phenyl sulfone moiety and molecular docking for VEGFR-2 kinase

  2021cites this paper
• On the important transition of sugar-based surfactant as a microreactor for C-S coupling in water: From micelle to vesicle

  2021cites this paper
• Gold(I)-Catalyzed Synthesis of 3-Sulfenyl Pyrroles and Indoles by a Regioselective Annulation of Alkynyl Thioethers

  2021cites this paper
• Synthesis of 3‐Methylthioindoles via Intramolecular Cyclization of 2‐Alkynylanilines Mediated by DMSO / DMSO ‐ d 6 and SOCl 2

  2021cites this paper
• Tandem micellar catalysis and cloud point extraction process for C-S coupling reaction in water

  2021cites this paper
• BF3-OEt2 Catalyzed C3-Alkylation of Indole: Synthesis of Indolylsuccinimidesand Their Cytotoxicity Studies

  2021cites this paper
• Review of the syntheses and activities of some sulfur-containing drugs.

  2020cites this paper
• Synthesis of mono and bis-substituted asymmetrical compounds, (1-(pyridin-2-yl)ethylidene)carbonohydrazide and 1-(2'-hydroxybenzylidene)-5-(1'-pyridylethylidene)carbonohydrazone: Structural characterization and antioxidant activity study

  2020cites this paper
• Visible-Light-Induced Cyclization/Aromatization of 2-Vinyloxy Arylalkynes: Synthesis of Thio-Substituted Dibenzofuran Derivatives.

  2020cites this paper
• A brief review of the biological potential of indole derivatives

  2020cites this paper
• Recent advances in photo-irradiated synthesis of bioactive heterocycles

  2020cites this paper
• The direct C3 chalcogenylation of indolines using a graphene-oxide-promoted and visible-light-induced synergistic effect

  2020cites this paper
• Visible‐Light Cercosporin Catalyzed Sulfenylation of Electron‐Rich Compounds with Thiols under Transition‐Metal‐Free Conditions

  2020cites this paper
• Synthesis and biological activities of novel trifluoromethylpyridine amide derivatives containing sulfur moieties

  2020cites this paper
• Metal-free C-S coupling of thiols and disulfides.

  2020cites this paper
• Convenient and Efficient Synthesis of Functionalized 2-Sulfenylindoles

  2020cites this paper
• Flavin/I2 -Catalyzed Aerobic Oxidative C-H Sulfenylation of Aryl-Fused Cyclic Amines

  2020cites this paper
• Pyrroles and Their Benzo Derivatives: Applications

  2020cites this paper
• Iodine/Manganese Catalyzed Sulfenylation of Indole via Dehydrogenative Oxidative Coupling in Anisole

  2020cites this paper
• Newly synthesized 3-sulfenylindole derivatives from 4-hydroxydithiocoumarin using an oxidative cross dehydrogenative coupling reaction (OCDCR): potential lead molecules for antiproliferative activity.

  2020cites this paper
• Palladium-catalyzed three-component cascade arylthiolation with aryldiazonium salts as S-arylation sources.

  2020cites this paper
• Synthetic strategies, SAR studies, and computer modeling of indole 2 and 3-carboxamides as the strong enzyme inhibitors: a review

  2020cites this paper
• Bisindolemethane derivatives as highly potent anticancer agents: Synthesis, medicinal activity evaluation, cell-based compound discovery, and computational target predictions

  2020cites this paper
• Photoredox Catalysis toward 2-Sulfenylindole Synthesis through a Radical Cascade Process.

  2020cites this paper
• Benzimidates as gem-Diamidation and Amidoindolyzation Cascade Synthons with a Hydrated NiII Catalyst.

  2020cites this paper
• Iodine-Catalyzed Synthesis of 3-Arylthioindoles Employing a 1-Aryltriazene/CS2 Combination as a New Sulfenylation Source

  2020cites this paper
• C-H Sulfonylation via 1,3-Rearrangement of Sulfonyl Group in N-protected 3-Bissulfonimidoindole Derivatives Using Fluorine Reagent.

  2020cites this paper
• Temperature-controlled regioselective thiolation of 2-indolylmethanols under aqueous micellar conditions

  2020cites this paper
• NH4I/1,10-phenanthroline catalyzed direct sulfenylation of N-heteroarenes with ethyl arylsulfinates

  2019cites this paper
• 3-Selenocyanate-indoles as new agents for the treatment of superficial and mucocutaneous infections

  2019cites this paper
• Recent advances in photocatalytic C–S/P–S bond formation via the generation of sulfur centered radicals and functionalization

  2019cites this paper
• Synthesis, spectroscopic, computational and drug docking studies of 1-(benzenesulfonyl)-2-methyl-1H-indole-3-carbaldehyde

  2019cites this paper
• Graphene oxide mediated thiolation of indoles in water: a green and sustainable approach to synthesize 3-sulfenylindoles

  2019cites this paper
• Hydrogen‐Bonding‐Network‐Assisted Regioselective Trifluoromethylthiolation and Sulfenylation of Electron‐Rich (Hetero)arenes

  2019cites this paper
• Domino C−S/C−N Bond Formation Using Well‐Defined Copper‐Phosphine Complex Catalyst: Divergent Approach to 3‐Sulfenylated Indoles

  2019cites this paper
• I2O5 promoted iodosulfenylation of indoles under metal-free conditions

  2019cites this paper
• Metal‐Free, Facile Synthesis of Sulfenylated Chromones and Indoles Promoted by an Aqueous HBr−DMSO System

  2019cites this paper
• Ultrasound Assisted Solvent/Metal Free Synthesis of 3‐Sulfenylindoles Employing TBATB‐Grafted MCM‐48 as a suitable Heterogeneous Catalyst.

  2019cites this paper
• Metal- and photocatalyst-free synthesis of 3-selenylindoles and asymmetric diarylselenides promoted by visible light

  2019cites this paper
• Synthesis, Antibacterial Activity, and Cytotoxicity of Newly Synthesized N-Substituted 5,6-Dimethoxy-1H-indole Derivatives

  2019cites this paper
• Synthesis of Thioethers from Sulfonyl Chlorides, Sodium Sulfinates, and Sulfonyl Hydrazides

  2019cites this paper
• Discovery of novel indolylarylsulfones as potent HIV-1 NNRTIs via structure-guided scaffold morphing.

  2019cites this paper
• in   situ Formation of RSCl/ArSeCl and Their Oxidative Coupling with Enaminone Derivatives Under Transition‐metal Free Conditions

  2019cites this paper
• Green approach for the synthesis of 3‐methyl‐1‐phenyl‐4‐((2‐phenyl‐1H‐indol 3‐yl)methylene)‐1H‐pyrazole‐5(4H)‐ones and their DNA Cleavage, antioxidant, and antimicrobial activities

  2019cites this paper
• Synthesis, molecular docking and biological evaluation of 2-(thiophen-2-yl)-1H-indoles as potent HIV-1 non-nucleoside reverse transcriptase inhibitors.

  2019cites this paper
• Indolylarylsulfones, a fascinating story of highly potent human immunodeficiency virus type 1 non-nucleoside reverse transcriptase inhibitors

  2018cites this paper
• Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wild-type and E138K mutant virus.

  2018cites this paper
• Synthesis and Antibacterial Activity of Novel 1H‐indol‐2‐ol Derivatives

  2018cites this paper
• Metal Free Mono- and 2,3-Bis-sulfenylation of Indoles in Water with Sodium Sulfinates as a Sulfur Source

  2018cites this paper
• Synthesis and anticholinesterase activity of 2-substituted-N-alkynylindoles.

  2018cites this paper
• Convenient synthesis of 2-amino-3-(arylthio)indoles via the Rh-catalyzed reaction of 3-diazoindol-2-imines with thioesters.

  2018cites this paper
• QSAR studies of indoyl aryl sulfides and sulfones as reverse transcriptase inhibitors

  2018cites this paper
• Catalyst-free sulfenylation of indoles with sulfinic esters in ethanol

  2018cites this paper
• Copper-catalysed regioselective sulfenylation of indoles with sodium sulfinates

  2018cites this paper
• An efficient t-BuOK promoted C3-chalcogenylation of indoles with dichalcogenides.

  2018cites this paper
• Recent Advances in the Design and Development of Non‐nucleoside Reverse Transcriptase Inhibitor Scaffolds

  2018cites this paper
• TEMPO-Catalyzed Aerobic Oxidative Selenium Insertion Reaction: Synthesis of 3-Selenylindole Derivatives by Multicomponent Reaction of Isocyanides, Selenium Powder, Amines, and Indoles under Transition-Metal-Free Conditions.

  2018cites this paper
• Visible‐Light‐Mediated Eosin Y Photoredox‐Catalyzed Vicinal Thioamination of Alkynes: Radical Cascade Annulation Strategy for 2‐Substituted‐3‐sulfenylindoles

  2018cites this paper
• I2-Catalyzed sulfenylation of indoles and pyrroles using triethylammonium thiolates as sulfenylating agents.

  2017cites this paper
• Iodine‐Catalyzed Mono‐ and Disulfenylation of Indoles in PEG400 through a Facile Microwave‐Assisted Process

  2017cites this paper
• Discovery of novel piperidine-substituted indolylarylsulfones as potent HIV NNRTIs via structure-guided scaffold morphing and fragment rearrangement.

  2017cites this paper
• Chiral Indolylarylsulfone Non-Nucleoside Reverse Transcriptase Inhibitors as New Potent and Broad Spectrum Anti-HIV-1 Agents.

  2017cites this paper
• Visible-light promoted synthesis of 3-arylthioindoles from indoles and diaryl disulfides

  2017cites this paper
• Copper-catalyzed synthesis of 2-sulfenylindoles from indoline-2-thiones and aryl iodides

  2017cites this paper
• Synthesis and biological activity of novel sulfone derivatives containing a [1,2,4]triazolo[4,3-a]pyridine moiety

  2017cites this paper
• Microwave assisted metal-/oxidant-free cascade electrophilic sulfenylation/5-endo-dig cyclization of 2-alkynylanilines to generate diversified 3-sulfenylindoles

  2017cites this paper
• Photocatalytic direct C–S bond formation: facile access to 3-sulfenylindoles via metal-free C-3 sulfenylation of indoles with thiophenols

  2017cites this paper
• Metal-free, iodine-catalyzed regioselective sulfenylation of indoles with thiols

  2016cites this paper
• A tetra-n-butylammonium iodide mediated reaction of indoles with Bunte salts: efficient 3-sulfenylation of indoles under metal-free and oxidant-free conditions.

  2016cites this paper
• Collective Synthesis of 3-Acylindoles, Indole-3-carboxylic Esters, Indole-3-sulfinic Acids, and 3-(Methylsulfonyl)indoles from Free (N-H) Indoles via Common N-Indolyl Triethylborate.

  2016cites this paper
• Novel indole sulfides as potent HIV-1 NNRTIs.

  2016cites this paper
• Catalytic Synthesis of 3-Thioindoles Using Bunte Salts as Sulfur Sources under Metal-Free Conditions.

  2016cites this paper